This proposal describes studies to specifically determine which blood elements in the coagulation cascade are activated by surface contact in extracorporeal perfusion systems. We will quantitate the initial changes in coagulation proteins of the intrinsic coagulation system caused by surface contact. We will study platelet membrane receptors and secreted proteins to determine the mechanism of platelet dysfunction caused by surface contact. We will define the activation and release of procoagulant substances by white cells. We will study specific inhibitors such as corn inhibitor, kininogen antibody, prostacyclin and lidocaine as well as ionically bonded herparin in an effort to selectively inhibit coagulation within extracorporeal perfusion systems without systemic herparin. Development of means selectively inhibit coagulation within extracorporeal perfusion systems will permit coagulation in wounds during perfusion, reduce morbidity due to released platelet and white cell granules and greatly extend clinical applications of extracorporeal perfusion systems for intermediate-term circulatory and respiratory support.